Basic science and translational research: recommendations from the Fifth International Consultation for Sexual Medicine (ICSM 2024).

Abstract

Introduction: Sexual function is a critical issue for human health and impacts the quality of life of patients and their partners. In this ICSM report, basic science and translational perspectives have been examined from the past decade of literature since the last ICSM report, and have been integrated to produce a state of the art summary of the physiology and molecular biology of sexual function/dysfunction and development of novel nanotechnology-based vehicles and treatments to aid regeneration and clinical translation in men and women.

Objectives: Examine, critically assess, and curate the most important and impactful basic and translational research findings on male and female sexual dysfunction since 2015.

Methods: Literature reviews were performed by a multidisciplinary committee of sexual medicine experts between June 2023 through May 2024. Findings were presented at the ICSM meeting in Madrid (June 2024), and comments from the consultation were incorporated to develop this consensus report.

Results: Erectile dysfunction (ED), which accompanies prostatectomy, diabetes, aging, and vascular disease in men, develops through both common and distinct mechanisms that involve neural injury, penile remodeling (smooth muscle (SM) apoptosis and increased collagen/fibrosis), dysregulated SM contractility, increased oxidative stress, immune response, and genomic instability. In women, disorders of genital pain, arousal, sexual desire, and orgasm involve multiple, overlapping neurological and endocrine mechanisms. Research on ED has been more extensive and the underlying molecular mechanisms have been better characterized than female sexual dysfunction. Future research directions should focus on pathways that underlie penile tissue remodeling and fibrosis associated with cavernous nerve injury in prostatectomy and diabetes, since this leads to irreversible ED. Particular emphasis should be placed on therapeutic targets to improve/enhance nerve regeneration, neuroprotection, "on demand" sexual function, SM contractility/relaxation, oxidative stress, immune response, and hormone function. In women, despite the existence of approved and off-label treatments for disorders of sexual desire and orgasm, the greater influence of psychosocial factors for these aspects of sexual function demands a multidisciplinary approach, along with predictive animal models. Genome-wide association studies have great potential in advancing the field but require replication and functional validation of findings from bioinformatic analyses. Progress in nanotechnology and regenerative therapies offers an exciting frontier in the targeted delivery of ameliorative/restorative treatments.

Conclusions: Research in sexual medicine has expanded through accelerated rates of discovery and increased breadth and diversity. However, much work remains in translating preclinical findings into biomarkers and clinical therapies that can improve patient outcomes.